To determine the association of cervical infections and their treatment on HIV-RNA cervical shedding among HIV-infected women on ART.

Setting

Research study site in Mombasa, Kenya

Study Design

Prospective cohort

Population

HIV-infected women on ART

Methods

HIV-seropositive women in the Mombasa Cohort were followed prospectively from 2004-2008 for incident cervical infections, starting one month after they initiated ART.(5) Women were followed monthly to identify cervical infections [gram stain and culture for Neisseria gonorrhoeae (NG) and non specific cervicitis (NSC), and to measure cervical HIV-RNA shedding. Every 3 months, cervical swabs were tested for NG and Chlamydia trachomatis (CT) using nucleic acid amplification (Gen Probe); blood samples were taken for CD4 cell counts. NSC was defined as ≥30 polymorphonuclear leukocytes on microscopy of cervical swab samples. NG was treated with norfloxacin; CT was treated with doxycycline; NSC was treated with both drugs; other symptomatic genital infections were treated syndromically according to national guidelines. One month following treatment, women were evaluated for 'test of cure.' Generalized estimating equations were used to compare the presence of cervical HIV-RNA above and below the detectable level (100 copies per swab) at the pre-cervicitis visit, versus during infection and after successful treatment. Multivariable models adjusted for hormonal contraceptive use, menstrual cycle stage, and duration on ART.

Results

Among the 147 women on ART who were followed, 30 women contributed 31 successfully treated incident cervical infections (13 NSC, 17 NG, and 1 CT). The median age of women with cervicitis was 36 yrs; median time on ART was 15 months and median CD4 cell count at the pre-infection visit was 308 cells/µl. Among the 30 women, cervical HIV-RNA was detected in one (407 copies/swab) at the pre-cervicitis visit, among 5 (median 115 copies/swab, range 100-820) at the cervicitis visit, and among 3 (657 copies/swab, range 110-1770) at the post-cervicitis visit. Among the 5 women who had detectable HIV-RNA with cervicitis, all except one had reduced HIV-RNA cervical shedding one month following treatment. The one woman with detectable HIV RNA pre-cervicitis, continued to have detectable HIV-shedding post treatment. Another woman had a marked increase in cervical HIV-shedding following treatment. This woman's ART adherence when diagnosed with cervicitis was 95% based on pill count, compared to the other women, whose ART adherence was 100%.

Conclusions

The authors conclude that among women on ART, the majority have undetectable cervical HIV-RNA even in the presence of cervical infections. Nevertheless, cervicitis can increase HIV-RNA cervical shedding, although the levels were low and near the limit of detection. The prevalence of detectable HIV, however, did not return to the pre-cervicitis baseline at the one-month visit after treatment, and may represent a gradual decline in shedding.

Study Quality

This was a good study, and allowed the collection of prospective data on incident cervical infections. However, the conclusions are limited by the small sample size, the few women who had cervical infections, the lack of CD4 data among those women with cervicitis and detectable HIV-RNA, and the lack of data on changes in cervical HIV-RNA at intervals longer than one month following treatment.

In Context

Most other studies have looked at the relationship of cervical shedding and cervicitis among HIV infected women who were not on antiretroviral therapy (ART). One study showed that HIV cervical shedding is high among women with cervicitis who are not on ART (11,220 copies/swab) and is reduced with successful treatment of cervical infections (1738 copies/swab).(1) A reduction in genital shedding may be gradual following treatment, as demonstrated in men treated for urethritis, in which there was a gradual reduction in seminal HIV-1 post-treatment.(2) Higher genital HIV RNA levels are likely associated with increased HIV transmission risk, as shown in a study of HIV-serodiscordant couples.(3) Together, these data argue for reduced overall transmission risk with ART treatment, which was found in a systematic review of sero-discordant couples on ART (reduced HIV transmission risk by 92% compared to those in which the HIV-positive partner was untreated).(4)

Programmatic Implication

Even among women on ART, detection and treatment of cervicitis remains important, as cervical infections can increase HIV-shedding. Although the cervical HIV-shedding was comparatively low in this study, even some cervical shedding can result in HIV transmission. This study adds data to an increasing body of evidence that treatment with ART reduces the risk of HIV transmission, and 5

therefore can be useful prevention strategy. Conclusions about the relationship of treatment and cervical infections were limited here, however, because of the small sample size. In addition, the authors did not provide information on whether the CD4 counts among women who had cervical shedding were higher than those who did not have detectable cervical HIV levels, which would have strengthened the understanding of the relationship of treatment to HIV infectivity.